fibrinopeptide-a and Pulmonary-Embolism

Topics: Biomarkers; Blood Coagulation Tests; Cerebral Infarction; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Fibrinopeptide B; Humans; Immunoenzyme Techniques; Myocardial Infarction; Peptide Fragments; Pulmonary Embolism; Radioimmunoassay; Thrombophilia; Venous Thrombosis

Thromboembolic disease continues to plague mankind because it is often detected too late for effective management, because modern therapeutic measures are often inefficiently managed, and because new therapeutic agents and available laboratory tests are ignored. New investigations that continue to be reported in Seminars in Thrombosis and Hemostasis and other journals deserve greater recognition and appreciation. Physicians and other scientists have reached a point at which antithrombotic and hemorrhagic effects of therapeutic anticoagulants can become dissociated if they effectively work together at the many interfaces for research and development among them to harvest the yield of basic research for practical clinical application.

Topics: Antithrombins; Blood Coagulation Tests; Factor X; Factor Xa; Fibrinopeptide A; Heparin; Humans; Intracranial Embolism and Thrombosis; Myocardial Infarction; Oligosaccharides; Prothrombin; Pulmonary Embolism; Thromboembolism

Topics: Animals; Antithrombin III; Biological Availability; Biotransformation; Blood Coagulation Tests; Chemical Phenomena; Chemistry; Disease Models, Animal; Drug Evaluation; Drug Stability; Factor X; Factor Xa; Fibrinolysis; Fibrinopeptide A; Hemorrhage; Heparin; Humans; Kinetics; Prothrombin; Pulmonary Embolism; Structure-Activity Relationship; Thrombophlebitis

Topics: Chemical Phenomena; Chemistry; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Humans; Kidney Diseases; Kinetics; Methods; Pulmonary Embolism; Solubility; Thrombin; Thrombophlebitis

Fibrinogen plays a pivotal role in both the humoral and cellular mechanisms involved in hemostasis. In performing its hemostatic function, fibrinogen in turn is acted on by several independent enzyme systems that either modify its structure or cleave specific fragments of the molecule into the surrounding milieu. Measurements of enzymatically modified fibrinogen or its proteolysis products represent a means whereby the action of these specific enzymes can be quantitated both in vitro and in vivo. Advances in such techniques as protein purification, affinity chromatography, peptide synthesis, and radioimmunoassay technology permit the translation of recently acquired primary structural data on this important protein into sensitive and specific assays for its circulating derivatives. These assay systems are important tools for probing mechanisms of hemostasis and thrombosis.

Topics: Ancrod; Blood Coagulation Tests; Chemical Phenomena; Chemistry, Physical; Chromatography, Gel; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Humans; Kinetics; Leukocytes; Peptide Hydrolases; Pulmonary Embolism; Thrombin; Thrombophlebitis

Topics: Disseminated Intravascular Coagulation; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Lupus Erythematosus, Systemic; Pulmonary Embolism; Radioimmunoassay; Thrombin; Thrombophlebitis

To determine the diagnostic and prognostic value of fibrinopeptides in patients with clinically suspected pulmonary embolism (PE), we made a pilot study in the Emergency Department with a general ICU. 32 patients with clinically suspected pulmonary embolism were the participants and 16 cases were diagnosed as PE-positive. After the diagnosis of PE, thrombolytic therapy with urokinase was administered, followed by heparin therapy. Plasma fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (FPB beta 15-42) were measured before treatment and at 1, 2 and 6 days after treatment. In the PE-positive patients, the levels of both fibrinopeptides measured prior to the treatment were above the normal values, and were significantly higher than those of PE-negative patients. When the cutoff points of FPA and, FPB beta 15-42 were set at 15 ng/ml, 15 ng/ml respectively, both markers had a high sensitivity, a highly negative predictive value and a moderate specificity. Six of the PE-positive patients died. The FPB beta 15-42 levels were significantly lower in the survivors than those in the patients who died at 2 days (p = 0.0092) and 6 days (p = 0.0011). We can conclude that: 1) the fibrinopeptide measured in this study are useful for screening for PE; and 2) FPB beta 15-42 may possibly be useful as a method for predicting the clinical outcome of PE.

Topics: Biomarkers; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Fibrinopeptide B; Humans; Peptide Fragments; Pilot Projects; Predictive Value of Tests; Prognosis; Prospective Studies; Pulmonary Embolism; Reference Values

Patients with heparin-induced thrombocytopenia urgently requiring surgery with cardiopulmonary bypass (CPB) present a unique management challenge that must be addressed by the use of alternative anticoagulants. Although clinical success with the direct thrombin inhibitor hirudin has been reported, there is sparse information in the literature supporting the efficacy of this drug as an anti-thrombotic to prevent fibrin formation during CPB. In this report, we describe the efficacy of this drug to prevent thrombin-mediated fibrin formation during CPB.

Topics: Adult; Anticoagulants; Cardiopulmonary Bypass; Chondroitin Sulfates; Contraindications; Dermatan Sulfate; Endarterectomy; Fibrinolytic Agents; Fibrinopeptide A; Heparin; Heparitin Sulfate; Hirudins; Humans; Hypertension, Pulmonary; Hypothermia, Induced; Male; Peptide Fragments; Postoperative Complications; Prothrombin; Pulmonary Embolism; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Thrombectomy; Thrombin; Thrombosis

Compared with the therapy of venous thromboembolism, there is little consensus regarding guidelines for heparin anticoagulation of patients with arterial thrombosis. This study aimed to identify the quantitative differences in the activation of the coagulation cascade and platelets in these two syndromes and to characterize their specific biological responses to heparin therapy.. Eighteen patients receiving intravenous heparin to treat venous (n = 9) or arterial (n = 9) thromboembolism were prospectively studied for an average of 4 days each. Clinical responses to treatment, activated partial thromboplastin time (aPTT), and molecular markers for thrombosis were measured regularly. Although both groups received equivalent doses of heparin (approximately 1100 units/h), the resulting aPTTs and plasma heparin activity were significantly lower in the arterial patients (P < .05 and P < .01, respectively). The plasma levels of beta-thromboglobulin (a marker for platelet activation and granule release) were significantly higher in the arterial patients (109 +/- 9.5 versus 79 +/- 7.1 ng/mL, mean +/- SEM, P < .05). In vivo fibrin formation, as evidenced by plasma levels of fibrinopeptide A, was less effectively suppressed in the patients with arterial versus venous thrombosis (18.5 +/- 3.2 versus 10.4 +/- 2 ng/mL, P < .05). Prothrombin fragments 1 + 2, a marker for prothrombinase complex activity, was nearly normal in both heparinized groups.. The anticoagulant response to heparin is blunted in patients with arterial thrombosis, at least in part by the antagonistic actions of increased platelet activation. Comparing arterial with venous thrombosis, higher doses of heparin on the average may be required to achieve comparable aPTTs, plasma heparin activity, and comparable suppression of fibrin formation.

Topics: Aged; beta-Thromboglobulin; Enzyme-Linked Immunosorbent Assay; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Partial Thromboplastin Time; Peptide Fragments; Prospective Studies; Protein Precursors; Prothrombin; Pulmonary Embolism; Thrombosis

This pilot study assessed the urinary fibrinopeptide A (uFPA) levels and the combination of uFPA test plus ventilation/perfusion (V/Q) scan in the diagnostic evaluation of acute pulmonary embolism (PE). One hundred consecutive patients were studied prospectively. Twenty-nine patients fulfilled diagnostic criteria defined in this study (seven with and 22 without PE). The uFPA concentration was significantly higher in patients with than without PE (41.1 +/- 2.6 vs 4.8 +/- 2.5 ng/mg of creatinine, p less than 0.0001). In all patients with PE, the uFPA levels were higher than threshold value derived by adding 2 standard deviations to the mean uFPA concentration of patients without PE. In patients without PE, the V/Q scan was negative in 16, the uFPA test was negative in 18, and at least one of the tests was negative in 21. These preliminary data suggest that a negative uFPA test may be helpful in excluding PE and that uFPA in combination with V/Q lung scans may correctly exclude PE in more patients than either test alone. Further studies in a large unselected population are needed to confirm these results.

Topics: Acute Disease; Adult; Aged; Angiography; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Pilot Projects; Probability; Prospective Studies; Pulmonary Embolism; Radionuclide Imaging; Sensitivity and Specificity; Technetium Tc 99m Aggregated Albumin; Ventilation-Perfusion Ratio

Topics: Adult; Aged; Aged, 80 and over; Erythrocyte Aggregation; Fibrin; Fibrinogen; Fibrinopeptide A; Humans; Methods; Middle Aged; Pulmonary Embolism; Thromboembolism

Fibrinopeptide A becomes free after thrombolysis of fibrinogen in thrombo-embolic situation. In view to quantify this molecule, the authors have compared two different methodologies (enzymatic and isotopic). Isotopic scintigraphy of lung (ventilation-perfusion) served as reference in this study for pulmonary thrombosis.

Topics: Enzyme-Linked Immunosorbent Assay; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Organotechnetium Compounds; Pentetic Acid; Pulmonary Embolism; Radioimmunoassay; Radionuclide Imaging; Technetium Tc 99m Pentetate; Time Factors

Topics: Fibrinogen; Fibrinopeptide A; Hirudins; Humans; In Vitro Techniques; Pulmonary Embolism; Thrombin

Indices of fibrinogen cleavage by thrombin (fibrinopeptide A, FPA); by plasmin (BB1-42 and serum FDP); of the platelet release reaction (beta thromboglobulin and platelet factor 4); and antithrombin III (AT III) levels were measured serially in 46 patients with pulmonary emboli in whom either substantial (SR) or impaired (IR) resolution was documented. The mean FPA level in the 25 patients with IR was significantly higher than the level in the 21 patients with SR (p less than 0.01). The increased thrombin activity in the IR group was not due to AT III deficiency or increased platelet reactivity but the elevated FPA levels in the presence of therapeutic levels of anticoagulation indicated that the dose of heparin was inadequate. The higher BB1-42 and FDP levels in this group reflected the increased plasmin activity that follows increased thrombin activity. In a multivariate discriminant analysis, only the FPA data could be used to predict the degree of resolution. Increased thrombin action impairs resolution presumably by producing greater amounts of accreted fibrin on the impacted embolus.

Topics: Antithrombin III; beta-Thromboglobulin; Fibrin; Fibrinogen; Fibrinolysin; Fibrinopeptide A; Heparin; Humans; Platelet Aggregation; Platelet Factor 4; Pulmonary Embolism; Thrombin

In 22 patients with suspected pulmonary embolism and 19 patients with suspected deep vein thrombosis, thrombin-antithrombin III complex (TAT) as an indicator of thrombin activation was measured using a newly developed ELISA. For comparison fibrinopeptide A (FPA), as a marker of an activated coagulation, as well as platelet factor 4 (PF4), and beta-thromboglobulin (beta-TG), as markers of platelet activation, were determined. In all patients in whom pulmonary embolism was confirmed by perfusion lung scan and in 15 of 16 patients in whom deep vein thrombosis was confirmed by phlebography, TAT exceeded the upper limit of normal (3.0 ng/ml). FPA was increased in 71% of the pulmonary embolism patients, PF4 in 53%, and beta-TG in 59%. The data for the patients with deep vein thrombosis were comparable. PF4 and beta-TG were increased in more than 25% of the normal controls, FPA in 17%, and TAT in 9%. TAT is very sensitive in detecting an activation of the coagulation system in patients with suspected thromboembolic events. The test, however, is not specific for thromboembolism; it only indicates an activation of the coagulation system. Acute pulmonary embolism or deep vein thrombosis would appear to be unlikely if TAT is normal. The measurement of TAT is easier and less susceptible to disturbances than that of FPA, PF4, and beta-TG.

Topics: Antithrombin III; beta-Thromboglobulin; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Platelet Factor 4; Pulmonary Embolism; Thrombin; Thrombophlebitis

The assay of fibrinopeptide A (FPA) has stimulated particular interest because of its high sensitivity and unique specificity for the action of thrombin. It has proved to be an extremely useful tool in research studies concerning the pathophysiology of thrombotic disease. Use of FPA in the diagnosis and treatment of deep venous thrombosis and pulmonary embolism is reviewed, and the potential usefulness of measuring FPA in the monitoring of the effectiveness of anticoagulant therapy is discussed.

Topics: Blood Preservation; Fibrinogen; Fibrinopeptide A; Humans; Pulmonary Embolism; Specimen Handling; Thrombophlebitis; Thrombosis

The purpose of this study was to assess the predictive values of the assays of fibrinopeptide A (FPA), beta-thromboglobulin (BTG) and their combination in patients suspected of having acute deep venous thrombosis (DVT) or pulmonary embolism (PE). In 80 controls the mean (+/- SD) plasma concentrations of FPA and BTG were 0.72 +/- 0.47 and 28.2 +/- 10.1 ng/ml, respectively. In 26 patients in whom DVT was confirmed by phlebography and Doppler ultrasound, clearly raised mean FPA (5.62 ng/ml) and BTG (70.6 ng/ml) concentrations were measured compared to those in 13 patients in whom this disorder was excluded (1.00 and 33.6 ng/ml, respectively). Also in 25 patients, in whom PE was established by perfusion lung scanning, clearly increased mean FPA (6.28 ng/ml) and BTG (82.4 ng/ml) concentrations were measured compared to those in 12 patients without this disease (1.03 and 32.5 ng/ml, respectively). Raised FPA and BTG concentrations were also found in 20 patients with inflammatory disorders and in 10 with various types of malignancy. The mean FPA and BTG concentrations did not differ between patients with renal failure or diabetes mellitus and patients without these diseases. From the predictive values of these assays and their combination it can be concluded that raised FPA and BTG concentrations are not specific for thrombosis. However, when normal FPA and BTG concentrations are present, acute DVT or PE can safely be excluded in symptomatic patients. In the group with confirmed DVT/PE, anticoagulant treatment (heparin and phenprocoumon) brought down the mean FPA concentration to levels within the normal range in less than 1 hour while the mean BTG concentration remained elevated throughout the 10-day study period.

Topics: Acute Disease; Adult; Aged; Beta-Globulins; beta-Thromboglobulin; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Middle Aged; Pulmonary Embolism; Thrombophlebitis

Topics: Acute Disease; Adult; Aged; Beta-Globulins; beta-Thromboglobulin; Fibrinogen; Fibrinopeptide A; Follow-Up Studies; Humans; Middle Aged; Pulmonary Embolism; Thrombophlebitis; Time Factors

The prompt reduction of elevated fibrinopeptide A (FPA) levels (normal less than 1.3 pmole/ml) by heparin therapy in patients with thromboembolism suggests that measuring the FPA level may provide a good index of disease activity and be a useful method of monitoring therapy. Sepsis or malignancy may elevate FPA levels and coexist with thromboembolism. FPA levels were surveyed in 51 patients with thromboembolism (including 15 with concurrent sepsis or malignancy) during heparin treatment in an attempt to distinguish the effects of coexistent disease and the progression of thromboembolism. The anticoagulant effect of heparin was within the therapeutic range for 81% of the study period. In patients with thromboembolism alone and marked resolution of emboli on repeat lung scan, the mean daily FPA levels were lower than the values in patients with minimal resolution (p less than 0.005). In patients with marked resolution of pulmonary embolism or venous thrombosis and a concurrent disorder, the mean FPA level remained elevated compared to normal values in patients with thromboembolism alone. These results suggest that FPA levels monitored during heparin therapy of thromboembolism may be useful as an index of disease activity except in the presence of coexisting sepsis or malignancy.

Topics: Adenocarcinoma; Adult; Aged; Anticoagulants; Carcinoma, Squamous Cell; Female; Fibrinogen; Fibrinopeptide A; Heart Failure; Heparin; Humans; Leukemia, Lymphoid; Lupus Erythematosus, Systemic; Male; Middle Aged; Polycythemia Vera; Pulmonary Embolism; Sepsis; Thromboembolism

Topics: Fibrinogen; Fibrinopeptide A; Humans; Pulmonary Embolism; Thrombophlebitis; Thrombosis